Background: Omega-3 polyunsaturated fatty acids (omega3-PUFAs) from fish oil (FO) reduce heart rate in humans. The mechanism underlying this cardioprotective effect of FO is unknown.
Objective: We studied the effects of an FO diet on heart rate, pacemaker activity, and pacemaker current (I(f)) in sinoatrial node (SAN) cells.
Methods: Rabbits were fed a diet enriched with 2.5% (w/w) FO or 2.5% high oleic sunflower oil (SO) as control for 3 weeks. Heart rate was measured in Langendorff-perfused hearts. Pacemaker activity and I(f) were recorded using the perforated patch-clamp technique in isolated SAN cells.
Results: In SAN cells, the FO diet reduced I(f) density by approximately 30%, without changes in its voltage dependence, reversal potential, (de)activation kinetics, and sensitivity to beta-stimulation. Dietary FO significantly prolonged the cycle length in both isolated perfused hearts (337 +/- 8 [mean +/- SEM, n = 8] vs. 301 +/- 9 ms [n = 8]) and single cells (363 +/- 20 [n = 19] vs. 276 +/- 8 ms [n = 22]). In single cells, dietary FO significantly decreased the diastolic depolarization rate by 33% and prolonged the action potential by 27%, whereas other action potential parameters were unaltered. I(f) blockade experiments substantiated that the reduced diastolic depolarization rate in the FO group was partially caused by the I(f) density reduction.
Conclusion: An FO diet prolongs the sinus cycle length because of, at least in part, a reduction in I(f) density. Our results explain FO-induced heart rate reduction and suggest FO as an alternative or adjunct to I(f)-lowering drugs.